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DISC1 条件 GWAS 分析在大型芬兰出生队列中精神分裂症倾向。

DISC1 conditioned GWAS for psychosis proneness in a large Finnish birth cohort.

机构信息

Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.

出版信息

PLoS One. 2012;7(2):e30643. doi: 10.1371/journal.pone.0030643. Epub 2012 Feb 17.

Abstract

BACKGROUND

Genetic evidence implicates the DISC1 gene in the etiology of a number of mental illnesses. Previously, we have reported association between DISC1 and measures of psychosis proneness, the Revised Social Anhedonia Scale (RSAS) and Revised Physical Anhedonia Scale (RPAS), in the Northern Finland Birth Cohort 1966 (NFBC66). As part of the studies of this Finnish birth cohort genome-wide association analysis has recently been performed.

METHODOLOGY

In the present study, we re-analyzed the genome-wide association data with regard to these two measures of psychosis proneness, conditioning on our previous DISC1 observation. From the original NFBC66 sample (N = 12 058), 4 561 individuals provided phenotype and genotype data. No markers were significant at the genome-wide level. However, several genes with biological relevance to mental illnesses were highlighted through loci displaying suggestive evidence for association (≥3 SNP with P<10E-4). These included the protein coding genes, CXCL3, KIAA1128, LCT, MED13L, TMCO7, TTN, and the micro RNA MIR620.

CONCLUSIONS

By conditioning a previous genome-wide association study on DISC1, we have been able to identify eight genes as associating to psychosis proneness. Further, these molecules predominantly link to the DISC1 pathway, strengthening the evidence for the role of this gene network in the etiology of mental illness. The use of quantitative measures of psychosis proneness in a large population cohort will make these findings, once verified; more generalized to a broad selection of disorders related to psychoses and psychosis proneness.

摘要

背景

遗传证据表明 DISC1 基因与多种精神疾病的病因有关。此前,我们曾报道过 DISC1 与精神病倾向的测量指标之间存在关联,即修订后的社会快感缺乏量表(RSAS)和修订后的身体快感缺乏量表(RPAS),这些关联是在 1966 年芬兰北部出生队列(NFBC66)中发现的。作为该芬兰出生队列研究的一部分,最近进行了全基因组关联分析。

方法

在本研究中,我们重新分析了与这两种精神病倾向测量指标相关的全基因组关联数据,条件是我们之前的 DISC1 观察结果。从原始的 NFBC66 样本(N=12058)中,有 4561 人提供了表型和基因型数据。没有标记在全基因组水平上具有显著意义。然而,通过显示出与关联(≥3 SNP,P<10E-4)相关的提示性证据的基因座,突出了几个与精神疾病具有生物学相关性的基因。这些基因包括编码蛋白的基因 CXCL3、KIAA1128、LCT、MED13L、TMCO7、TTN 和 microRNA MIR620。

结论

通过在 DISC1 上对以前的全基因组关联研究进行条件化,我们能够确定 8 个基因与精神病倾向有关。此外,这些分子主要与 DISC1 途径相关,进一步证明了该基因网络在精神疾病病因学中的作用。在大人群队列中使用精神病倾向的定量测量指标,一旦得到验证,将使这些发现更广泛地适用于与精神病和精神病倾向相关的广泛的疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91e9/3281861/e19c962286a5/pone.0030643.g001.jpg

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